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1.
Artigo em Inglês | MEDLINE | ID: mdl-34515544

RESUMO

ARST1321, a trial of patients with advanced soft tissue sarcoma, was the first National Clinical Trials Network study codeveloped by pediatric and adult consortia with two treatment cohorts. We report on the findings of a survey to identify barriers to enrolling adolescent and young adult patients (15-39 years) onto the nonchemotherapy arm. The survey response rate was 31% with a 70% completion rate. Common identified reasons for low accrual in order of decreasing frequency included insufficient funding, lack of study awareness or interest, competing trials, toxicity concerns, philosophical differences in the therapy backbone, and regulatory and infrastructure barriers. Clinical Trials.gov ID: NCT02180867.

2.
J Clin Med ; 10(7)2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33915882

RESUMO

Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children's Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.

3.
J Adolesc Young Adult Oncol ; 10(1): 66-70, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32460587

RESUMO

Purpose: To evaluate the availability of fertility preservation (FP) services and educational resources on the websites of top-ranked U.S. pediatric cancer programs. Methods: Cross-sectional survey of information and resources related to FP on websites from top-ranked pediatric cancer programs according to the 2018-2019 U.S.-News & World Report (USNWR) ranking. Factors that predicted the website availability of FP information or a fertility team were analyzed, as was availability in Spanish and for specific groups by sex and puberty status. As a surrogate marker of comprehensive oncological services, the availability of resources for psychological support was compared to FP. Results: A fertility team was referenced on the website of 36% of programs, but only 32% provided FP educational resources for patients. Among them, 100%, 93.8%, 93.8%, and 68.8% provided specific information for postpubertal females, prepubertal females, postpubertal males, and prepubertal males, respectively. The majority (93.8%) did not provide information in Spanish. The ranking on USNWR (p < 0.05) and patient volume (p < 0.05) positively correlated with the availability of FP information and fertility team on the program's website. Information regarding psychological support was provided more often than information regarding FP (96% vs. 32%, p < 0.05). Conclusion: The majority of the top-ranked pediatric cancer programs in the United States do not list FP resources or a fertility team on their website. The lack of resources is particularly concerning for the Spanish-speaking population, as well as for prepubertal males. This may be potentially hindering access to FP and contributing to health care disparities.

4.
Pediatr Blood Cancer ; 68(3): e28871, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33381908

RESUMO

The scarcity of adequate pediatric drug labeling information has long been problematic in the pediatric population, which may place children at risk for adverse drug effects. The ontogeny of infants, children, and adolescents over the course of the first two decades of life pose complex pharmacokinetic, dosing, administration, effectiveness, and toxicity-related questions that require specific investigation. Here, we review the history that led to the passage of the Best Pharmaceuticals for Children Act (BPCA) and Pediatric Research Equity Act (PREA), and provide commentary on issues relevant to pediatric oncology now and in the future.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Legislação de Medicamentos/normas , Neoplasias/tratamento farmacológico , Preparações Farmacêuticas/administração & dosagem , Vigilância de Produtos Comercializados/métodos , Criança , Regulamentação Governamental , Humanos , Estados Unidos , United States Food and Drug Administration
5.
J Pediatr Hematol Oncol ; 42(8): 474-481, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32282650

RESUMO

The Ewing sarcoma family of tumors (ESFT) are high-grade small round blue cell malignancies traditionally presenting in children and adolescents. The most common site of primary disease is bone, though extraskeletal primary sites are well-recognized. We present 6 cases of primary ESFT of the kidney and 1 case of the adrenal gland. Patients were 11 to 18 years of age at diagnosis. Metastases at diagnosis were present in most cases (n=6). All patients underwent surgery, and most received radiation (n=5). Five patients relapsed after initial remission. Comprehensive review of the primary renal ESFT literature was used to analyze various factors, including age, sex, disease metrics, metastases at diagnoses, and overall survival in a total of 362 cases. Notably, while the general ESFT population has reported rates of metastasis at diagnosis of 20% to 25%, this rate in the renal ESFT population was 53% with a rate of 59% in adolescent and young-adult patients (11 to 24 y). Nodal disease at diagnosis was present in 24% of renal ESFT cases compared with 3.2% in patients with primary skeletal ESFT. While this malignant process may share histologic and molecular features with its bone and soft tissue counterparts, primary renal ESFT presentations seem to be more aggressive and have worse outcomes.


Assuntos
Neoplasias Renais/patologia , Sarcoma de Ewing/patologia , Adolescente , Criança , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Sarcoma de Ewing/genética , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/terapia
6.
Cancer ; 125(20): 3514-3525, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31355930

RESUMO

Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.


Assuntos
Epigenômica , Genômica , Osteossarcoma/terapia , Pesquisa Médica Translacional , Criança , Humanos , Mutação/genética , Osteossarcoma/epidemiologia , Osteossarcoma/genética , Osteossarcoma/patologia , Proteômica , Proteína Supressora de Tumor p53/genética
7.
Pediatr Blood Cancer ; 66(4): e27579, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30548185

RESUMO

One of the limitations of performing percutaneous biopsies in patients with bone sarcomas is the small amount of tumor that can be obtained for research purposes. Here, we describe our experience developing patient-derived tumor xenografts (PDXs) using percutaneous tumor biopsies in children with bone sarcomas. We generated 14 bone sarcoma PDXs from percutaneous tumor biopsies. We also developed eight bone sarcoma PDXs from surgical resection of primary bone tumors and pulmonary metastases. A multidisciplinary team approach was critical to establish an accurate diagnosis and to provide adequate tumor samples for PDX generation.


Assuntos
Neoplasias Ósseas , Neoplasias Pulmonares , Osteossarcoma , Adolescente , Adulto , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Criança , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Masculino , Metástase Neoplásica , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/terapia , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Pediatr Blood Cancer ; 65(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29049857

RESUMO

PURPOSE: To determine the impact of surgery and/or radiation therapy on distant metastatic sites (DMS) in children with stage IV rhabdomyosarcoma (RMS). METHODS: A retrospective chart review was conducted on all patients with stage IV RMS at Texas Children's Hospital from 1992 to 2012. Data analyzed included age, gender, primary site, histologic subtype, number and sites of metastases, treatment including local therapy to DMS, and Oberlin score. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 20% and 25%. The 5-year PFS in patients receiving local therapy to all DMS (n = 16) and to less than all DMS (n = 19) was 31.3% versus 0% (P = 0.002), whereas the 5-year OS was 37.3% versus 0% (P < 0.001), respectively. The 5-year PFS in patients with isolated lung metastasis versus other types of metastasis was 29% versus 7% (P = n.s.), whereas the 5-year OS was 43% versus 10% (P = 0.01). The 5-year pulmonary local control was improved by the use of whole lung irradiation (WLI; 56% vs. 10%, P = 0.03). CONCLUSIONS: Local treatment to all metastatic sites was associated with improved PFS and OS at 5 years. The use of WLI improved pulmonary control in patients with lung metastasis. We recommend an aggressive approach including local therapy to DMS in children with stage IV RMS.


Assuntos
Neoplasias Pulmonares , Rabdomiossarcoma , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/radioterapia , Rabdomiossarcoma/cirurgia , Taxa de Sobrevida
11.
Methods Mol Biol ; 1699: 113-118, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29086373

RESUMO

Circulating microRNAs are increasingly being used as noninvasive prognostic and predictive biomarkers for various types of cancer. We describe a method that uses real-time quantitative PCR (qPCR) for establishing a signature plasma microRNA profile that can distinguish patients with osteosarcoma from healthy control samples.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Ósseas/diagnóstico , Perfilação da Expressão Gênica/métodos , MicroRNAs/sangue , Osteossarcoma/diagnóstico , Biomarcadores Tumorais/genética , Neoplasias Ósseas/sangue , Feminino , Humanos , MicroRNAs/genética , Osteossarcoma/sangue , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
12.
Oncotarget ; 8(57): 96738-96752, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29228567

RESUMO

Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who have a poor response to chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients. In this study, we examined whether circulating miRNAs can be used as biomarkers in osteosarcoma patients. We performed genome-wide miRNA profiling on a discovery cohort of osteosarcoma and control plasma samples. A total of 56 miRNAs were upregulated and 164 miRNAs were downregulated in osteosarcoma samples when compared to control plasma samples. miR-21, miR-221 and miR-106a were selected for further validation based on their known biological importance. We showed that all three circulating miRNAs were expressed significantly higher in osteosarcoma samples than normal samples in an independent cohort obtained from the Children's Oncology Group. Furthermore, we demonstrated that miR-21 was expressed significantly higher in osteosarcoma tumors compared with normal bone controls. More importantly, lower expressions of miR-21 and miR-221, but not miR-106a, significantly correlated with a poor outcome. In conclusion, our results indicate that miR-21, miR-221 and miR-106a were elevated in the circulation of osteosarcoma patients, whereas tumor expressions of miR-21 and miR-221 are prognostically significant. Further investigation of these miRNAs may lead to a better prognostic method and potential miRNA therapeutics for osteosarcoma.

13.
Pediatrics ; 140(1)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28759392

RESUMO

A 3-week-old boy, former 39-week term infant, presented to the emergency department with a rash. One week before presentation, he developed dark, purple papules on his forehead, which then spread to the abdomen and inguinal regions. Throughout this time, he was eating well, gaining weight, developing appropriately, and was afebrile without cough, congestion, or rhinorrhea. On presentation, the patient was well appearing with normal vital signs. His weight was 4.83 kg (86th percentile for age), his length was 56 cm (47th percentile for age), and his head circumference was 37 cm (62nd percentile for age). On skin examination, there were scattered purpuric papules and macules on the scalp, forehead, trunk, abdomen, and inguinal region. Initial laboratory studies were remarkable only for mild anemia. Our expert panel examines the case, offers a differential for a child with a "blueberry muffin" rash, and makes diagnostic considerations.


Assuntos
Exantema/diagnóstico , Pele/patologia , Mirtilos Azuis (Planta) , Diagnóstico Diferencial , Humanos , Recém-Nascido , Masculino
14.
Int J Cancer ; 141(10): 2062-2075, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28748534

RESUMO

Ewing Sarcoma (ES) is a highly aggressive bone tumor with peak incidence in the adolescent population. It has a high propensity to metastasize, which is associated with dismal survival rates of approximately 25%. To further understand mechanisms of metastasis we investigated microRNA regulatory networks in ES. Our studies focused on miR-130b due to our analysis that enhanced expression of this microRNA has clinical relevance in multiple sarcomas, including ES. Our studies provide insights into a novel positive feedback network involving the direct regulation of miR-130b and activation of downstream signaling events contributing toward sarcoma metastasis. Specifically, we demonstrated miR-130b induces proliferation, invasion, and migration in vitro and increased metastatic potential in vivo. Using microarray analysis of ES cells with differential miR-130b expression we identified alterations in downstream signaling cascades including activation of the CDC42 pathway. We identified ARHGAP1, which is a negative regulator of CDC42, as a novel, direct target of miR-130b. In turn, downstream activation of PAK1 activated the JNK and AP-1 cascades and downstream transcriptional targets including IL-8, MMP1 and CCND1. Furthermore, chromatin immunoprecipitation of endogenous AP-1 in ES cells demonstrated direct binding to an upstream consensus binding site within the miR-130b promoter. Finally, small molecule inhibition of PAK1 blocked miR-130b activation of JNK and downstream AP-1 target genes, including primary miR-130b transcripts, and miR-130b oncogenic properties, thus identifying PAK1 as a novel therapeutic target for ES. Taken together, our findings identify and characterize a novel, targetable miR-130b regulatory network that promotes ES metastasis.


Assuntos
Neoplasias Ósseas/patologia , Proteínas Ativadoras de GTPase/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/secundário , MicroRNAs/genética , Sarcoma de Ewing/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Retroalimentação Fisiológica , Proteínas Ativadoras de GTPase/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Estadiamento de Neoplasias , Prognóstico , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Transdução de Sinais , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína cdc42 de Ligação ao GTP/genética , Proteína cdc42 de Ligação ao GTP/metabolismo , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo
15.
Genes Chromosomes Cancer ; 54(12): 796-808, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26355645

RESUMO

Osteosarcomas (OSs) are characterized by high levels of genomic instability (GI). To gain insights into the GI and its contribution toward understanding the genetic basis of OS, we characterized 19 primary and 13 metastatic mouse tumors in a genetically engineered novel mouse model of OS by a combination of genomic techniques. Through the bone-specific deletion of the wild-type Trp53 locus or activation of a metastatic-promoting missense R172Hp53 allele, C57BL/6 mice developed either localized or metastatic OS. Subsequent tumors were isolated and primary cultures created from primary bone and/or distal metastatic lesions, for example, lung and liver. These tumors exhibited high levels of GI with complex chromosomal rearrangements, amplifications, and deletions comparable to human OS. The combined genomic approaches identified frequent amplification of chromosome 15D1 and loss of 11B4 by CGH and/or SKY. Both 15D1 and 11B4 have homology with frequently altered chromosomal bands 8q24 and 17p13 in human OS, respectively. Subsequent array CGH, FISH, and qRT-PCR analysis identified coamplification and overexpression of Myc/Pvt1 transcripts from the 15D1 amplicon and loss and decreased expression of the Nlrp1b from 11B4. The Nlrp1 gene is the key mediator of apoptosis and interacts strongly with caspase 2.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Neoplasias Ósseas/genética , Osteossarcoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante/genética , Sarcoma Experimental/genética , Proteína Supressora de Tumor p53/genética , Animais , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Ósseas/patologia , Caspase 2/metabolismo , Deleção Cromossômica , Amplificação de Genes , Loci Gênicos , Instabilidade Genômica , Homozigoto , Hibridização in Situ Fluorescente , Cariotipagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação de Sentido Incorreto , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Osteoblastos/metabolismo , Osteossarcoma/patologia , Cultura Primária de Células , Sarcoma Experimental/patologia , Regulação para Cima
16.
Cancer Med ; 4(7): 977-88, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25784290

RESUMO

Osteosarcoma (OS) is the primary bone tumor in children and young adults. Currently, there are no reliable, noninvasive biologic markers to detect the presence or progression of disease, assess therapy response, or provide upfront prognostic insights. MicroRNAs (miRNAs) are evolutionarily conserved, stable, small noncoding RNA molecules that are key posttranscriptional regulators and are ideal candidates for circulating biomarker development due to their stability in plasma, ease of isolation, and the unique expressions associated with specific disease states. Using a qPCR-based platform that analyzes more than 750 miRNAs, we analyzed control and diseased-associated plasma from a genetically engineered mouse model of OS to identify a profile of four plasma miRNAs. Subsequent analysis of 40 human patient samples corroborated these results. We also identified disease-specific endogenous reference plasma miRNAs for mouse and human studies. Specifically, we observed plasma miR-205-5p was decreased 2.68-fold in mice with OS compared to control mice, whereas, miR-214, and miR-335-5p were increased 2.37- and 2.69-fold, respectively. In human samples, the same profile was seen with miR-205-5p decreased 1.75-fold in patients with OS, whereas miR-574-3p, miR-214, and miR-335-5p were increased 3.16-, 8.31- and 2.52-fold, respectively, compared to healthy controls. Furthermore, low plasma levels of miR-214 in metastatic patients at time of diagnosis conveyed a significantly better overall survival. This is the first study to identify plasma miRNAs that could be used to prospectively identify disease, potentially monitor therapeutic efficacy and have prognostic implications for OS patients.


Assuntos
Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , MicroRNAs/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Transcriptoma , Adolescente , Adulto , Aloenxertos , Animais , Biomarcadores Tumorais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/terapia , Criança , Modelos Animais de Doenças , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/sangue , Estadiamento de Neoplasias , Osteossarcoma/mortalidade , Osteossarcoma/terapia , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
17.
Int J Radiat Oncol Biol Phys ; 90(4): 858-62, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25245583

RESUMO

PURPOSE: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. METHODS AND MATERIALS: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. RESULTS: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). CONCLUSIONS: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.


Assuntos
Neuroblastoma/diagnóstico por imagem , Neuroblastoma/radioterapia , 3-Iodobenzilguanidina/farmacocinética , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Quimioterapia de Consolidação/métodos , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Humanos , Quimioterapia de Indução/métodos , Lactente , Neoplasia Residual , Neuroblastoma/metabolismo , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
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